This invention relates to a method of quantitatively measuring and monitoring color values and changes in the iris of an eye. Iris coloration may be affected by many factors--some related to disease or to administered medications, especially those useful for conditions of the eye. For example, members of the class of pharmaceutical compositions known as prostaglandins have known therapeutic activity in reducing intraocular pressure and are, therefore, regarded as a promising medication for glaucoma. One example is the prostaglandin known commonly as latanoprost (isopropyl-(Z)-7[(1R,2R,3R,5S)3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpent yl]cyclo-pentyl]-5-heptenoate), which is commercially available from Pharmacia & Upjohn under the trademark XALATAN.TM.. It is generally well-tolerated, systemically and in the eye. However, one side effect of administration of this prostaglandin compound, especially in larger primates and man, is increased pigmentation of the iris of the eye. This effect was found, for example, in about 5% to 15% of Cynomolgus monkeys in multi-center clinical trials.
This effect appears mainly in mixed color eyes such as blue-brown, green-brown, yellow-brown, and grey-brown, and may result in a darker iris. The effect has not been noted in dark-brown irises. The first changes in pigmentation generally occur after three months of prostaglandin treatment. In monkeys with yellow-green eyes, a dose-dependent increase in pigmentation was noted after 3-12 months of topical prostaglandin administration. This side effect may be cosmetically undesirable, and may be indicative of other concerns relating to therapeutic treatment of a patient to whom such iris color-effecting medications are administered.
The long-term effect and the mechanism for this adverse reaction are not entirely known. Some studies have indicated that stimulation of melanin production, rather than proliferation of melanocytes may be a cause. While it is not known if all prostaglandins exhibit this effect, another example currently being tested is isopropyl unoprostone, marketed under the trade name RESCULA.RTM..
We have discovered that iris coloration can be quantitatively determined so that changes in iris coloration can be monitored quantitatively over time. Hence, in the case of naturally- or drug-induced iris color changes, the progress of the causative condition or therapy can be correspondingly monitored. The method has applicability in pharmacology and toxicology as well as in the monitoring of patients treated with anti-glaucoma medications.
It is known conventionally to compare iris color to a known standard color scale by visual observation of the iris side-by-side with the standard (which can be incorporated into the photograph). However, it is generally necessary to record the iris coloration by photograph; and color changes in photographs over time, as well as differences in development chemistry from film sample to film sample, make difficult if not impossible the reliable long-term monitoring of the same iris. Such changes in development, for example, ordinarily require that each photograph be developed manually and calibrated to a color scale which must be included on the photograph along with the object.
Hence, such methodology is generally expensive, complicated, time-consuming and unreliable. Further, the visual observer's perceptive eyesight is inherently problematic and the results necessarily subjective. Even discounting these natural handicaps, evaluation of approximate eye color by comparison against a standard color scale cannot be more than a rough visual integration of the average pigmentation of the evaluation area.